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Pharmacological effects and clinical evaluation of toludesvenlafaxine in the treatment of depression LI Yumeng, DU Xiaoyu, QIU bo, WU Huizhen Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 419-426.   DOI: 10.12092/j.issn.1009-2501.2025.03.016 Abstract （1314）      PDF （954KB）（782）       Knowledge map    Save Depression is a common mental disease. At present, there are poor efficacy and drug-related safety problems in antidepressant treatment. Toludesvenlafaxine, as a new triple reuptake inhibitor (TRIs/SNDRIs), increases the inhibitory effect of dopamine (DA) reuptake on the basis of serotonin (5-HT) and norepinephrine (NE), achieves multi-target synergistic therapy and reduces 5-HT/NE-related adverse drug reactions. This article reviews the basic introduction, preclinical research, clinical efficacy and safety of toludesvenlafaxine, in order to provide more ideas and options for the treatment of depression. Related Articles | Metrics

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Targeting the cGAS-STING pathway for the treatment of ischemic stroke  QIAN Qingfang, LI Wenjing, LI Qiang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 690-694.   DOI: 10.12092/j.issn.1009-2501.2025.05.013 Abstract （735）      PDF （770KB）（1631）       Knowledge map    Save Ischemic stroke is a devastating neurological disease worldwide, with high global burden. The microglial activation-driven neuroinflammation plays a critical role in pathophysiology of ischemic stroke. After the ictus of brain ischemic attack, cytosolic double-stranded DNA (dsDNA) released by necrotic neuronal cells is a potential damage-associated molecular pattern (DAMP) to activate cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. cGAS-STING signaling pathway has emerged as a key player in microglial activation, sterile neuroinflammation, and cell death following ischemic stroke. Targeting this pathway holds promise for developing novel therapeutics that effectively mitigate neuroinflammation, prevent cell death, and enhance patient outcomes. In this review, we first outline the principal elements of the cGAS-STING signaling cascade, then discusses the pivotal role of the cGAS-STING pathway in ischemic stroke. Then, we outline selective small-molecules modulators that function as cGAS-STING inhibitors and summarize their mechanisms to treat Ischemic stroke. Finally, we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.  Related Articles | Metrics

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Clinical efficacy of Tirellizumab combined with lenvatinib in the treatment of advanced liver cancer WU Yuanyuan, LI Chenlu, CHEN Yan, CAO Mengda, SHAO Hua Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 392-397.   DOI: 10.12092/j.issn.1009-2501.2025.03.012 Abstract （710）      PDF （642KB）（424）       Knowledge map    Save AIM: To investigate the efficacy and safety of checkpoint inhibitor lenvatinib combined with Tirelizumab in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was performed on 52 patients with advanced HCC treated with Renvatinib, tirellizumab or their combination from January 2021 to December 2022 in Zhongda Hospital Affiliated to Southeast University, with disease progression, death and intolerance as endpoints. Efficacy was assessed according to RECIST 1.1 criteria and follow-up was conducted up to June 2023. The main endpoints of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival, PFS) and security. RESULTS: The combination therapy significantly improved ORR and mPFS in patients compared with tirelizumab or lenvatinib monotherapy. Compared with single tirellizumab or lenvastinib, there was no significant difference in the adverse reactions associated with the combination treatment, suggesting that the combination of the two was generally well tolerated and the side effects are controllable. CONCLUSION: Lonvastinib combined with tirelizumab is more effective in the treatment of HCC, can significantly prolong PFS, and is generally well tolerated, which may be a potential treatment for advanced HCC. Related Articles | Metrics

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Research progress on the addictivity and neurotoxicity of ketamine ZI Zhian, ZHAO Tingyi, WANG Gongwu, CAO Jun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (9): 1233-1242.   DOI: 10.12092/j.issn.1009-2501.2025.09.010 Abstract （639）      PDF （676KB）（578）       Knowledge map    Save As a new type of rapid antidepressant, ketamine has provided a new approach for the treatment and research on the pathological mechanism of major depressive disorder. However, the addictive potential and neurotoxicity of ketamine have become issues that cannot be ignored in clinical medication. This article briefly introduces the relevant research progress on ketamine addiction and neurotoxicity mechanisms at home and abroad, hoping to provide a reference for the rational development and utilization of ketamine. Related Articles | Metrics

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SAS macro tool for pharmacokinetic parameter estimation based on non-compartmental models ZHANG Li, LOU Donghua Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 608-621.   DOI: 10.12092/j.issn.1009-2501.2025.05.004 Abstract （634）      PDF （706KB）（688）       Knowledge map    Save AIM: To develop a SAS macro tool for calculating pharmacokinetic (PK) parameters using non-compartmental analysis (NCA) that is applicable to various routes and frequencies of drug administration. METHODS: By incorporating the principles of NCA PK parameter calculations, the structure of the SAS macro program is designed and programmed. The usage of the macro program is demonstrated through simulated examples. RESULTS: Based on NCA, this study programmed a SAS macro using SAS macro language to calculate both single-dose and steady-state complete PK parameters. It supports three modes of drug administration: extravascular, intravenous infusion, and intravenous bolus injection, as well as four algorithms for calculating area under the curve (AUC). By comparing with authoritative calculation software, the results were found to be highly consistent across various calculation scenarios, with more accurate calculations for the time of first measurable concentration (Tlag). CONCLUSION: The %M_CREATE_PK_PARAMETERS macro is a SAS macro that supports comprehensive PK parameter calculations in NCA, providing an accurate, efficient, and flexible solution for PK parameter estimation with broad application prospects. Related Articles | Metrics

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Research progress of epigenetics in the pathogenesis of depression ZHANG Yao, ZOU Manshu, HAN Yuanshan, WANG Yuhong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 517-525.   DOI: 10.12092/j.issn.1009-2501.2025.04.010 Abstract （589）      PDF （924KB）（1289）       Knowledge map    Save Depression is a mental disease with increasing prevalence worldwide, which seriously endangers human health with high disability rate and high suicide rate. Epigenetics is an emerging genetic theory in the 21st century. Its main research content is to regulate the process of gene transcription or translation and affect its function and characteristics without changing the DNA sequence. These include DNA methylation, histone modification, chromatin remodeling and non-coding RNA regulation. The nervous system is susceptible to changes in the activity of epigenetic modifiers, and an increasing number of studies have shown that genetics and environment play an important role in the development of depression. This review will focus on the epigenetic mechanisms of depression. Related Articles | Metrics

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Clinical research progress of efgartigimod in the treatment of generalized myasthenia gravis LIU Shu, SUN Chunhui, TAN Zhirong, XING Man Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 714-720.   DOI: 10.12092/j.issn.1009-2501.2025.05.017 Abstract （573）      PDF （742KB）（836）       Knowledge map    Save Myasthenia gravis (MG) is a chronic autoimmune disease that causes partial or systemic skeletal muscle weakness and fatigue. Efgartigimod is an antibody fragment targeting the Fc receptor in newborns, which clears pathogenic immunoglobulin G antibodies through a unique mechanism. Efgartigimod is used to treat systemic myasthenia gravis safely and efficiently, which can significantly improve muscle strength and quality of life for patients. This article reviews pharmacological, clinical research, and safety of efgartigimod, in order to providing reference for its clinical treatment in systemic myasthenia gravis (gGM). Related Articles | Metrics

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New progress in the treatment of polycythemia vera  LI Yueming, ZHANG Yongchao, CHEN Fang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (7): 961-967.   DOI: 10.12092/j.issn.1009-2501.2025.07.011 Abstract （548）      PDF （738KB）（1135）       Knowledge map    Save Polycythemia vera (PV) is a type of BCR::ABL1 negative myeloproliferative neoplasms (MPN), which is a chronic myeloid tumor caused by gene mutations in hematopoietic stem cells. PV has a certain risk of progressing to myelofibrosis or acute myeloid leukemia. At present, the goal of PV treatment is still to prevent thrombosis. With the deepening of PV research, it is possible to transform the lifelong treatment to prevent the progression of the disease from alleviating the symptoms of patients. This article reviews the mechanism of traditional cytoreductive therapy drugs and the latest clinical trial results, as well as the early clinical trial data and their mechanism of action of new PV drugs and combination of drugs, in order to provide help for researchers who pay attention to PV treatment. Related Articles | Metrics

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Research progress on targeted drug delivery strategies in inflammatory lung diseases LI Xiaonan, LI Yang, XU Zhangxi, KANG Shuzhen, KONG Li, ZHANG Zhiping Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 313-324.   DOI: 10.12092/j.issn.1009-2501.2025.03.003 Abstract （545）      PDF （946KB）（849）       Knowledge map    Save Inflammatory lung diseases are currently a major challenge threatening human health and life. Imbalanced inflammation and excessive inflammation can lead to tissue damage and trigger the occurrence and development of systemic diseases. Anti-inflammatory treatment is of vital importance for improving patient survival and quality of life. In recent years, significant progress has been made in the exploration and research of drug targeting strategies, effectively addressing issues such as slow onset, low bioavailability, and rapid in vivo clearance rates during drug delivery. Drug targeting can increase local drug concentrations, reduce dosing frequency, and mitigate side effects. This review primarily elaborates on the classification and characteristics of inflammatory lung diseases. It comprehensively reviews targeted drug delivery strategies for inflammatory lung diseases from three perspectives: local targeting, passive targeting, and active targeting. Furthermore, it discusses the prospects and challenges of drug targeted therapy for lung diseases, potentially providing new research and application ideas for the targeted treatment of inflammatory lung diseases. Related Articles | Metrics

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Advances and future research prospects in regulatory policies for clinical trials of artificial intelligence medical devices LIANG Hao, WANG Shun, CUI Cheng, SONG Ling, SUN Ailin, LI Man, QIAO Jie, SONG Chunli, LI Haiyan, ZHAO Yangguang, LI Haiyan, ZHANG Chenguang, LIU Dongyang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 427-431.   DOI: 10.12092/j.issn.1009-2501.2025.03.017 Abstract （505）      PDF （581KB）（3889）       Knowledge map    Save Artificial intelligence (AI) has emerged as a cutting-edge technology leading the future and is a key engine for China's development. In the innovation and research of medical devices, AI has provided critical support in the areas of intelligent diagnostic assistance, intelligent therapeutic assistance, intelligent monitoring, life support, et al. Machine learning-enabled device software functions (ML-DSFs) have become an essential component of many medical devices. Recently, the United States Food and Drug Administration (FDA) released a draft guidance titled " Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions (Draft). " that aimed to provide a forward-looking approach to foster the development of ML medical devices. By supporting iterative updates through modifications, this approach ensures the continuous safety and effectiveness of the devices. This guidance represents the latest in regulatory direction and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI products. Therefore, we plan to provide a detailed introduction and interpretation of the guidance, with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence. Related Articles | Metrics

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Optimizing the dosing regimen of aripiprazole microspheres by population pharmacokinetic modeling and simulation MENG Qingheng, HAN Zhihui, LEI Qi, CHEN Bin, YIN Xia, HU Haitang, LIU Hongxia, ZHENG Qingshan, XU Ling, HUANG Qin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 493-500.   DOI: 10.12092/j.issn.1009-2501.2025.04.007 Abstract （494）      PDF （2366KB）（362）       Knowledge map    Save AIM: To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere (LZMT05) using plasma concentration data from two clinical trials. METHODS: Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05, and a population pharmacokinetic (PopPK) model was developed. The therapeutic window was defined as the steady-state trough-to-peak concentration range (94.0-534 ng/mL) of oral aripiprazole. Multiple clinical scenarios were simulated to identify the optimal regimen. RESULTS: A one-compartment model with dual first-order absorption and first-order elimination characterized LZMT05 pharmacokinetics. Covariates like sex and CYP2D6 genotype were integrated into the final model. Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 every 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations. CONCLUSION: The PopPK-guided optimized LZMT05 regimen maintained drug exposure within the therapeutic window, suggesting favorable efficacy and safety. Related Articles | Metrics

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Network pharmacological analysis of berberine inhibiting breast cancer cell proliferation and in vitro cell validation#br# ZHANG Huihui, JIN Le, LIU Su, CHEN Hongxiao, CHEN Zhaolin, TANG Liqin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 332-338.   DOI: 10.12092/j.issn.1009-2501.2025.03.005 Abstract （444）      PDF （1702KB）（192）       Knowledge map    Save AIM: To explore the mechanism of berberine on breast cancer cells based on network pharmacology and in vitro cell experiments. METHODS: Firstly, berberine and breast cancer were taken as the research objects, the intersection targets of the two were screened by VEEN diagram, GO function and KEGG enrichment analysis were performed by R language, and molecular docking and visualization were carried out by Autodock Vina and Pymol software. Then, berberine treated breast cancer MCF-7 cells for 24 h, and then in vitro cell experiments were performed. CCK-8 was used to detect cell viability, Edu and plate cloning were used to detect cell proliferation and cloning, and apoptosis was detected by An-nexin V-FITC/PI double staining and Western blot. Laser confocal and CETSA were used to verify the binding effect of berberine and AKT1 protein. RESULTS: The results of network pharmacology showed that berberine had a good binding to the core targets AKT1, AKT2 and MAPK3. Berberine (20, 40, 80 μmol/L) significantly inhibited the proliferation and cloning ability of MCF-7 cells in a concentration-dependent manner (P<0.05, P<0.01). The results of laser confocal and CETSA experiments showed that berberine and AKT1 had a binding effect, and the stability of the two was enhanced after the combination. CONCLUSION: Berberine inhibits MCF-7 cell proliferation and induces apoptosis in human breast cancer cells by targeting binding to AKT1 protein. Related Articles | Metrics

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Research progress of empagliflozin in the treatment of type 2 diabetes mellitus and cardiovascular and renal benefits LIU Zihan, DU Wenyu, GUO Caihui, WANG Zhi, LI Ying, DONG Zhanjun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 412-418.   DOI: 10.12092/j.issn.1009-2501.2025.03.015 Abstract （438）      PDF （952KB）（1767）       Knowledge map    Save Type 2 diabetes mellitus (T2DM) is an insulin resistance disease. Improving insulin resistance and controlling blood glucose are the main means of clinical treatment for T2DM. Empagliflozin is a highly selective sodium-dependent glucose transporters (SGLT)2 inhibitor, which is independent of insulin. It can effectively control blood glucose levels, reduce blood pressure and body weight, protect heart and kidney function, reduce the rehospitalization rate and the risk of death in patients with heart failure (HF), and does not increase the risk of hypoglycemia. Empagliflozin can be used alone or in combination with other hypoglycemic drugs to control blood glucose. This article reviews the mechanism of action, clinical benefits, and combination with other drugs of empagliflozin, aiming to provide reference for the clinical use of empagliflozin. Related Articles | Metrics

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Research progress on the clinical application and mechanism of commonly used traditional Chinese medicine in the treatment of breast cancer LI Shanshan, WEI Dandan, KANG Hanyu, LIU Xiaopeng, YAN Shuxun, JIANG Shiqing Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (7): 977-983.   DOI: 10.12092/j.issn.1009-2501.2025.07.013 Abstract （436）      PDF （988KB）（3574）       Knowledge map    Save Breast cancer is a common clinical gynecological tumor. According to the 2022 global cancer data statistics, breast cancer ranks second in terms of incidence among newly diagnosed cancer cases worldwide. Modern medicine often adopts surgical operation, chemotherapy, and other methods, which have certain efficacy but also many problems such as high drug resistance rates and significant adverse reactions. Chinese patent medicines exhibit extensive anticancer effects. The study found that Shenyi Capsule, Pingxiao Capsule, and Zhenqi Fuzheng Granules were widely used in the treatment of breast cancer, exerting therapeutic effects on breast cancer by inhibiting cell proliferation, invasion, and metastasis, suppressing angiogenesis, reversing cellular drug resistance, and inhibiting precancerous lesions. Meanwhile, the oral administration of Chinese patent medicines in combination with other traditional Chinese medicine (TCM) compounds, TCM decoctions, or modern medical treatments can improve patients' quality of life and reduce adverse reactions. Currently, there are numerous studies on the treatment of breast cancer with Chinese patent medicines, but a systematic summary is lacking. Therefore, this study conducted a systematic review of the mechanisms of action and clinical applications of Chinese patent medicines as adjuvant therapy for breast cancer, aiming to provide guidance for clinical medication. Related Articles | Metrics

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Expert consensus on the model informed precision dosing of tacrolimus in patients receiving anti-rejection therapy CHEN Bing, ZUO Xiaocong, LI Xingang, SHANG Dewei, ZHOU Peijun, DING Junjie, XIANG Xiaoqiang, QIU Xiaoyan, WANG Zhuo, LI Xiaoyu, ZHANG Yi, ZHAO Wei, WANG Yuzhu, GAO Jianjun, JIAO Zheng Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 433-445.   DOI: 10.12092/j.issn.1009-2501.2025.04.001 Abstract （429）      PDF （844KB）（1659）       Knowledge map    Save There is significant inter-individual variation of pharmacokinetics and pharmacodynamics in patients receiving tacrolimus (TAC) for anti-rejection therapy, which cause the rejection or toxic action. Based on results of therapeutic drug monitoring and pathophysiological index of transplant patients, the individualized dosing regimen can be designed and adjusted by using model informed precision dosing (MIPD). The patients' clinical outcome can be improved. In the consensus, the different methods of MIPD used for patients received TAC for anti-rejection therapy were introduced, which can be used for the designing and adjusting doing regimen, predicting adverse drug reaction, improving medication adherence and economics during therapy. Related Articles | Metrics

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Engineered bacteria modulate tumor-associated macrophages to enhance immunotherapy WANG Long, WANG Yuchen, GUO Yilin, WU Jinhui Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 297-312.   DOI: 10.12092/j.issn.1009-2501.2025.03.002 Abstract （426）      PDF （1338KB）（2459）       Knowledge map    Save The immunosuppressive tumor microenvironment significantly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs), the most abundant immune cells in the tumor microenvironment, often exhibit an immunosuppressive M2 phenotype, contributing to this immunosuppressive landscape. Modulating TAMs to adopt anti-tumor phenotypes can enhance immunotherapy outcomes and inhibit tumor progression.In recent years, tumor immunotherapy leveraging engineered bacteria has garnered considerable attention. Bacteria possess the ability to target tumors, preferentially colonizing tumor regions, and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment. This activation enhances the tumoricidal and clearance capabilities of TAMs. With the rapid advancements in synthetic biology, engineered bacteria have emerged as a potent therapeutic modality for immunotherapy, leading to increased focus on the regulation of TAMs by engineered bacteria.This paper first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor therapy. It then reviews recent advancements in bacterial regulation of TAMs, detailing how engineered bacteria enhance TAM recruitment, improve TAM phagocytosis, and remodel TAM phenotypes. Modulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy. Related Articles | Metrics

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Recent research progress of Menin inhibitors in NPM1-mutated acute myeloid leukemia YU Xiaoda, LI Jiajing, WANG Anan, GUO Jiangang, LIU Bei Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 533-540.   DOI: 10.12092/j.issn.1009-2501.2025.04.012 Abstract （422）      PDF （999KB）（345）       Knowledge map    Save The nucleophosmin 1 (NPM1) mutation is one of the most frequent subtypes in acute myeloid leukemia (AML). Under the conditions of FLT3-internal tandem duplications (FLT3-ITD) and/or DNMT3A co-mutations or adverse cytogenetics, the originally favorable prognosis will deteriorate. In recent years, studies have found that multiple endocrine neoplasia protein (Menin) inhibitors targeting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX (homeotic gene) and MEIS1 (myeloid ecotropic viral integration site 1) in NPM1-mutated AML, demonstrating remarkable anti-leukemia activity. This article aims to review the mechanism and clinical research of Menin inhibitors, novel small molecule targeted drugs in NPM1-mutated AML, as well as the resistance mechanism of Menin inhibitors, hoping to provide promising approaches for the subsequent treatment of NPM1-mutated AML patients.  Related Articles | Metrics

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Research progress on advanced therapeutic approaches and emerging technologies in the drug treatment of refractory thyroid cancer CHEN Hongdan, HUANG Yinde, LI Chong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 325-331.   DOI: 10.12092/j.issn.1009-2501.2025.03.004 Abstract （411）      PDF （845KB）（464）       Knowledge map    Save Poorly differentiated and advanced thyroid cancers are characterized by high malignancy, progress rapidly, and resistance to radiotherapy and chemotherapy. These characteristics pose significant challenges, severely limiting effective treatment options. Various kinase inhibitors have been used in the treatment of refractory thyroid cancer were used accompanying by the carcinogenic mechanisms' studies investigating in thyroid cancer, such as Dabrafenib (BRAF inhibitor), Trametinib (MEK inhibitor), Vandetanib (RET inhibitor), Lenvatinib (VEGF inhibitor), and multi-target kinase inhibitors. However, drug resistance remains an inevitable issue, significantly limiting the efficacy and application of kinase inhibitors. Therapeutic approaches such as immunotherapy, redifferentiation strategies for thyroid cancer, radiopharmaceutical conjugates, and the application of nanotechnology are currently in the clinical research stage, requiring further clarification of their efficacy. Comprehensive understanding of therapeutic strategies and available treatment combinations for refractory thyroid cancer is of paramount importance in the diagnosis and treatment of thyroid cancer. Therefore, this article reviews technologies and methods for treating refractory thyroid cancer, focusing on chemotherapy, molecular targeted therapy, immunotherapy, and radiopharmaceutical therapy, aiming to provide a reference for selecting treatment strategies for refractory thyroid cancer. Related Articles | Metrics

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The NO-sGC-cGMP pathway and heart failure LI Dilu, PEI Yuanyuan, WANG Wuchao, CAO Lingjie, YANG Fengtao, SHI Shuangkui, ZHOU Guyue, YANG Kunyu, ZHU Jihong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 702-708.   DOI: 10.12092/j.issn.1009-2501.2025.05.015 Abstract （407）      PDF （621KB）（2231）       Knowledge map    Save Heart failure, as a global public health challenge, is experiencing an increasingly severe disease burden. Given the close relationship between the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate (NO-sGC-cGMP) signaling pathway and heart failure, this study, through a comprehensive search and review of recent literature on the NO-sGC-cGMP pathway and heart failure, aims to outline the mechanism of action of this signaling pathway and its connection with heart failure, in order to explore new avenues for the treatment of heart failure. Related Articles | Metrics

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Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (11): 1440-.   Abstract （404）      PDF （3523KB）（67）       Knowledge map    Save Related Articles | Metrics

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Research progress on mechanism of action of Chaenomeles speciosa Nakai in the treatment of rheumatoid arthritis bone restruction CAO Jun, ZHOU Yanlin, AI Zhengwen, LI Shigang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 404-411.   DOI: 10.12092/j.issn.1009-2501.2025.03.014 Abstract （398）      PDF （800KB）（830）       Knowledge map    Save Rheumatoid arthritis is an autoimmune disease characterized by progressive bone destruction, with joint swelling caused by synovial inflammation in the early stage, and joint deformity caused by cartilage and bone destruction occurring in the middle and late stages as inflammation develops, resulting in a 75% disability and deformity rate within three years, and the prevention and treatment of RA bone and joint destruction is of urgency, and it is therefore of great significance to search for effective drugs to treat RA bone destruction. Studies have shown that wrinkled skin papaya can treat RA bone destruction, but the composition and mechanism of action are unknown, so this review aims to provide an overview of the mechanism of action of the effective active ingredients in wrinkled skin papaya for the treatment of rheumatoid arthritis bone destruction, and to provide a basis and direction for the development of novel formulations of traditional Chinese medicines for anti-RA bone destruction. Related Articles | Metrics

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Research progress of traditional Chinese medicine intervention in chemotherapy renal injury LIU Yeyuan, QI Yafeng, ZHANG Maofu, LI Xinyu, SHEN Yanyun, LIU Yu, ZHANG Shangzu, LI Yangyang, ZHANG Liying, ZHANG Zhiming Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 556-569.   DOI: 10.12092/j.issn.1009-2501.2025.04.015 Abstract （382）      PDF （843KB）（2988）       Knowledge map    Save Renal injury is one of the common adverse reactions in the clinical application of chemotherapy drugs, which is the main reason why the chemotherapy can not be carried out in the whole cycle. The pathological mechanism of chemotherapy-induced renal injury is very complicated, mainly involving oxidative stress, inflammatory response, apoptosis, mitochondrial dysfunction, and regulation of transporters, causing pathological damage to renal tubules or glomeruli. At present, there is no specific pharmacological intervention for the treatment of chemotherapy-induced renal injury. As a treasure of traditional Chinese medicine, traditional Chinese medicine has the advantages of overall regulation, multi-targeting, small adverse reactions and no obvious drug dependence in the prevention and treatment of chemotherapy-induced renal injury. In recent years, there have been more and more studies on the intervention of chemotherapy-induced renal injury by multi-component and multi-directional intervention of active components, extracts and compounds of traditional Chinese medicine, and some progress has been made. A large number of studies have shown that the potential mechanisms of traditional Chinese medicine in preventing and treating renal injury induced by chemotherapy include inhibiting oxidative stress, reducing inflammatory response and inhibiting apoptosis. Although there are many studies on the mechanism of action of traditional Chinese medicine in the treatment of chemotherapy-induced renal injury, there is still a lack of systematic review. Based on this, this paper summarizes the mechanism of renal injury induced by chemotherapy and the intervention of traditional Chinese medicine, so as to provide theoretical support for its clinical treatment and new drug innovation. Related Articles | Metrics

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SPP1 expression in SMARCA4-deficient non-small cell lung cancer and its relationship with PD-L1 WU Juan, HUANG Xi, LI Jiajia, WEI Yuqing, ZHANG Liqing, YU Yongmei, LU Zhiwei, ZHANG He Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 477-486.   DOI: 10.12092/j.issn.1009-2501.2025.04.005 Abstract （379）      PDF （1297KB）（1994）       Knowledge map    Save AIM: To analyze the expression of secreted phosphoprotein 1 (SPP1) and programmed cell death-ligand 1 (PD-L1) in SMARCA4-deficient non-small cell lung cancer, and to provide a scientific basis for the study of the follow-up treatment of this rare pathological type of lung cancer. METHODS: The clinical and pathological characteristics of 12 patients with this disease were analyzed retrospectively, and the patients were divided into two groups of adenocarcinomas and poorly differentiated carcinomas according to their morphological characteristics, and the relationship between the expression of SPP1 and PD-L1 was analyzed in the two groups. RESULTS: SPP1 expression was detected in all patients and Its expression level was significantly higher in the poorly differentiated carcinoma group compared with the adenocarcinoma group (P=0.015); PD-L1 expression was found in 6/7 patients (5 cases were not measured), compared with the adenocarcinoma group,PD-L1 was also highly expressed in the poorly differentiated carcinoma group (P=0.048) and the PD-L1 difference between the two groups suggested that the results were similar to those of SPP1. CONCLUSION: SMARCA4-deficient non-small cell lung cancer has high positive expression of SPP1 and PD-L1. It was more pronounced in patients with poorly differentiated carcinoma. There may be a positive correlation between SPP1 and PD-L1 expression in SMARCA4-deficient non-small cell lung cancer and the mechanism of the correlation needs to be further verified in subsequent studies. Related Articles | Metrics

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Effects of branched-chain and aromatic amino acids on type 2 diabetes mellitus and the progress ZHANG Mengli, WU Fangfang, TAN Zhien, OU Min, LIU Lingjie, LU Na, QIAO Liya, YANG Xiaonan Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 526-532.   DOI: 10.12092/j.issn.1009-2501.2025.04.011 Abstract （375）      PDF （1193KB）（604）       Knowledge map    Save Type 2 diabetes mellitus is a metabolic disease characterized by high blood sugar levels. Traditionally, amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis. However, in recent years, amino acids have gained increased attention as signaling molecules that play crucial roles in the maintenance and regulation of metabolic homeostasis. It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus. Furthermore, there have been successive reports on the regulation mechanism involved. This article will focus on the metabolic processes, mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus. It will also summarize and provide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus, with the aim of offering new ideas for the treatment of type 2 diabetes mellitus. Related Articles | Metrics

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Advances in pharmacokinetics of isavuconazole in special population XIE Jingxian, DU Jianjun, CHEN Lu, ZHANG Lijuan, YANG Yong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 709-713.   DOI: 10.12092/j.issn.1009-2501.2025.05.016 Abstract （373）      PDF （612KB）（387）       Knowledge map    Save Isavuconazole represents a novel generation of triazole antifungal agents for the treatment of invasive trichothecenes in adults. The pharmacokinetic profile of isavuconazole differs in special populations, including children, patients with extracorporeal membrane oxygenation, those with hepatic or renal injury, patients undergoing blood purification, and critically ill individuals and solid organ transplant recipients. These differences impact the safety and efficacy of patient treatment. This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations. Related Articles | Metrics

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Drug therapy and new technology progress of type 2 diabetes mellitus LIU Xing, CHEN Ying Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (9): 1215-1223.   DOI: 10.12092/j.issn.1009-2501.2025.09.008 Abstract （366）      PDF （665KB）（1149）       Knowledge map    Save As the incidence of diabetes in China continues to rise, its complications pose a serious threat to the life health of patients. New hypoglycemic agents are constantly emerging, with particular attention being paid to glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i), which can not only effectively control blood glucose levels, but also significantly improve the cardiac and renal outcomes of diabetic patients. New technologies for diabetes management based on artificial intelligence (AI) are also developing rapidly, playing a crucial role in the diagnosis of diabetic retinopathy (DR) and insulin dose-assisted decision-making. Continuous glucose monitoring (CGM) and automated insulin delivery system (AID) have already been used clinically. This article reviews the progress in drug therapy and new technologies for type 2 diabetes mellitus T2DM, aiming to provide guidance for the treatment of T2DM patients. Related Articles | Metrics

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Research progress on the role of macrophage polarization in cardiovascular diseases CUI Hanyu, HU Changping Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 548-555.   DOI: 10.12092/j.issn.1009-2501.2025.04.014 Abstract （363）      PDF （699KB）（2371）       Knowledge map    Save As phagocytic innate immune cells, macrophages interact with various tissue types and play an important role in immune defense, inflammatory response and tissue remodeling. Macrophages participate in the occurrence and development of disease by polarizing into classically activated M1 type and substitutively activated M2 type, or more complex phenotypes, when the tissue microenvironment changes. This paper focused on the application of macrophage polarization in cardiovascular diseases, and introduces macrophage origin and activation to propose the relationship between macrophage polarization and cardiovascular diseases. Then, the strategies for targeted macrophage therapy were proposed to provide an important theoretical basis for improving the inflammatory state of cardiovascular diseases. Related Articles | Metrics

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The role of platelets in tumor development and the treatments based on them LU Qi, DU Lili, SUN Jin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 290-296.   DOI: 10.12092/j.issn.1009-2501.2025.03.001 Abstract （356）      PDF （821KB）（995）       Knowledge map    Save The platelets play the important role in tumor angiogenesis, growth, and metastasis, in addition to coagulation. The interaction between tumors and platelets can produce "tumor-induced platelets", which leads various changes of platelet characteristics. In addition, activated platelets can also inhibit the effects of both chemotherapy and immunotherapy, therefore, both inhibiting platelet activation and depleting platelets can effectively improve tumor prognosis. In this review, we introduced the key role of platelets in the development of tumors, summarized their application in tumor diagnosis, monitoring, and treatment, and provided our view on how to develop precise delivery strategies based on platelets for achieve efficient and safe tumor treatment. Related Articles | Metrics

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Effects of liposomal bupivacaine for interscalene brachial plexus block on postoperative analgesia and diaphragmatic function in patients with arthroscopic rotator cuff repair surgery LUO Jingyu, WU Hong, CHEN Gang, XU Mengting, ZHANG Yantong, LI Jun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 665-672.   DOI: 10.12092/j.issn.1009-2501.2025.05.010 Abstract （353）      PDF （830KB）（1359）       Knowledge map    Save AIM: To evaluate the effects of liposomal bupivacaine for interscalene brachial plexus block on postoperative analgesia and diaphragmatic function in patients undergoing arthroscopic rotator cuff repair surgery based on a  randomized controlled trial. METHODS: Forty patients who scheduled to undergo arthroscopic rotator cuff repair surgery, regardless of gender, aged 18 to 65 years, ASA grade I or II were selected from October 2023 to February 2024. The patients were randomly divided into bupivacaine liposome group (group LB) and the levobupivacaine group (group BV), with 20 cases in each group. Patients in both groups received an ultrasound-guided interscalene brachial plexus block, 15 mL mixed liquids (bupivacaine liposome 10 mL+0.5% levobupivacaine 10 mL) were injected into the level of C5-C6 nerve roots and 5 mL onto the surface of prevertebral fascia in the LB group, and same volume of 0.375% levobupivacaine were injected at the same sites in the BV group respectively. Standardized general anesthesia and standardized postoperative analgesia were followed. The primary outcome measures included 48 h rest/motor numerical rating scale (NRS) scores after surgery and the incidence of hemidiaphragmatic paralysis (HDP) after block. The secondary outcome measures included rest/motor NRS scores at other time points after surgery, pulse oxygen saturation (SpO2) 30 min after block, duration of sensory and motor block, number of analgesic pump presses, time of first postoperative used of opioid drugs and opioid consumption, use of additional analgesics in the wards, satisfaction with analgesia, and the occurrence of perioperative adverse effects and neurological complications. RESULTS: Compared with group BV, patients in LB group showed lower rest NRS scores at 48 h postoperation (P<0.05) and higher incidence of HDP at 24 h after block (45% vs. 5.3%, P<0.05). However, there was no significant difference in motor NRS scores at 48 h, HDP incidence at 30 min and 6 h after block between the two groups (P>0.05). Both groups showed a decrease in SpO2 after block compared to before block (P<0.05). Compared with BV group, patients in LB group had a significantly longer duration of sensory and motor block (P<0.01), fewer effective presses with the analgesic pump (P<0.01), delay in first opioid use and less opioid consumption (P<0.05), higher level of satisfaction with analgesia (P<0.01), and a lower rate of use of additional analgesics in the ward (P<0.05). There was no statistically significant difference in the total intraoperative remifentanil consumption, incidence of perioperative adverse reactions and neurological complication between the two groups (P>0.05). CONCLUSION: Compared with using levobupivacaine alone, the addition of liposomal bupivacaine for interscalene brachial plexus block in arthroscopic rotator cuff repair can reduce postoperative NRS scores, decrease postoperative opioid dosage and significantly prolong blockduration, but can easily lead to longer duration of HDP in patients. Related Articles | Metrics

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Arecoline promotes oral submucous fibrosis by upregulating PI3K/Akt/mTOR signaling pathway in vivo and in vitro LIU Xun, ZHOU Tingting, ZHU Zibing, TAN Jin, LI Qun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (7): 865-875.   DOI: 10.12092/j.issn.1009-2501.2025.07.001 Abstract （347）      PDF （1510KB）（821）       Knowledge map    Save AIM：To explore the potential mechanism of arecoline in promoting oral submucous fibrosis based on key factors of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. METHODS: SD rats were randomly divided into arecoline low-dose group, arecoline medium-dose group, and arecoline high-dose group (5, 10, and 15 mg/mL). The oral buccal mucosa was injected with the corresponding concentration of arecoline (ANE) solution to induce the establishment of oral submucous fibrosis (OSF) models, with 8 rats in each group. Another 8 unmodeled rats were selected as the blank group, and the changes in mouth opening of the rats were detected after 8 weeks of grouping and intervention. HE and Masson staining were used to observe the pathological changes of oral buccal mucosa, measure the length of epithelial staple process and calculate collagen volume fraction. Western blot and qRT-PCR were used to detect the expression of collagen-Ⅰ (COL-I), E-cadherin, fibronectin (FN) and PI3K/Akt/mTOR signaling pathway-related proteins and mRNA in rat oral buccal mucosa.The levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and transforming growth factor (TGF) -β1 in rat serum were detected by ELISA. Human immortalized keratinocytes (HaCaT cell line) were cultured in vitro, and the effects of different concentrations of arecoline, PI3K activator, and PI3K inhibitor on the survival rate of HaCaT cells were investigated by CCK-8 method. According to the results of CCK-8, the concentration of arecoline 75 μg/mL, the concentration of PI3K activator 10 μmol/L, and the concentration of PI3K inhibitor 2 μmol/L were selected as the subsequent experimental concentrations. The cells were set as blank group, arecoline group, PI3K activator group, PI3K inhibitor group, and arecoline + PI3K inhibitor group. The mRNA expression levels of COL-I, E-cadherin, FN, PI3K, Akt, and mTOR in each group of cells were detected by qRT-PCR. The levels of TNF-α, IL-1β and TGF-β1 in each group of cells were detected by ELISA. RESULTS: Compared with the blank group, the arecoline low-dose group, the arecoline medium-dose group, and the arecoline high-dose group significantly reduced the mouth opening, significantly shortened the length of the epithelial staple process, significantly increased the collagen volume fraction, inflammatory cell infiltration, and severe pathological damage. The protein expression levels of COL-I, FN, p-PI3K, p-Akt, and p-mTOR were up-regulated, and the protein expression levels of E-cadherin were down-regulated. The mRNA expressions of COL-I, FN, PI3K, Akt, and mTOR were significantly increased. The mRNA expression of E-cadherin was significantly reduced, and the levels of TNF-α, IL-1β, and TGF-β1 were significantly increased (all P<0.05 or P<0.01). Compared with the blank group, the mRNA expression levels of COL-I, FN, PI3K, Akt, and mTOR in the cells of the arecoline group and the PI3K activator group were up-regulated, and the mRNA expression levels of E-cadherin were down-regulated. Compared with the blank group, the mRNA expression levels of COL-I, FN, PI3K, Akt, and mTOR in the cells of the PI3K inhibitor group were down-regulated, and the mRNA expression levels of E-cadherin were up-regulated. Compared with the PI3K inhibitor group, the mRNA expression levels of COL-I, FN, PI3K, Akt, and mTOR in the cells of the arecoline + PI3K inhibitor group were up-regulated, the mRNA expression levels of E-cadherin were down-regulated, and the levels of TNF-α, IL-1β, and TGF-β1 were significantly increased (all P<0.05 or P<0.01). CONCLUSION: Arecoline can significantly promote oral submucous fibrosis, which may play a pro-fibrotic role by upregulating the PI3K/Akt/mTOR signaling pathway. Related Articles | Metrics

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Study on the efficacy and mechanism of Qingre xiaoyanning against influenza A H3N2 virus ZHOU Shasha, CHENG Xueqing, PENG Dongdong, WANG Xiaoqing, FU Lijun, XIAO Wenxi, ZHANG Guomin Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 347-354.   DOI: 10.12092/j.issn.1009-2501.2025.03.007 Abstract （345）      PDF （1860KB）（1501）       Knowledge map    Save AIM: To investigate the antiviral efficacy and mechanism of Qingre Xiaoyanning (QRXYN) in vivo, and provide experimental basis for their prevention and treatment of influenza A virus. METHODS: We constructed a mouse model infected with influenza A H3N2 virus. To evaluate the therapeutic effect of QRXYN on influenza A virus, we measured the body weight changes, pathological changes in lung tissue, hemagglutination titer, and viral load in mouse. To evaluate the possible mechanism of QRXYN's anti influenza A virus infection, we used the ELISA to measure the levels of TNF-α, IL-1β, IL-4, IFN-γ, and vascular cell adhesion molecule-1 (VCAM-1) in mouse bronchoalveolar lavage fluid; used flow cytometry to assess the proportions of macrophages (F4/80), helper T lymphocytes (CD4+ T lymphocytes), and natural killer (NK) cells in lung tissue; and used Western blotting to detect the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MYD88), inhibitor of kappa B kinase-β (IKK-β), NF-kappa-B inhibitor alpha (IκBα), and phospho-IKB alpha (p-IκBα) in lung tissue. RESULTS: Compared to the model group, both Oseltamivir and QRXYN can alleviate the severity of lung tissue lesions in mice, decrease the blood coagulation titer and viral load of mouse lung tissue (P<0.01), lower the levels of TNF-α, IL-4, and VCAM-1 in bronchoalveolar lavage fluid (P<0.05, P<0.01), reduce the proportion of macrophages (P<0.05, P<0.01), and increase the proportion of CD4+T lymphocytes and NK cells (P<0.05, P<0.01). Additionally, oseltamivir can reduce the expression of MYD88 protein in mouse lungs (P<0.05), while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs (P<0.05). CONCLUSION: QRXYN have good in vivo antiviral effects against the influenza A virus, and their mechanism may be related to the regulation of the immunologic function and NF-κB signal pathway. Related Articles | Metrics

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Improvement of non-alcoholic steatohepatitis by Butein and research on its mechanism LIU Jing, HOU Kai, ZHANG Li Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 355-365.   DOI: 10.12092/j.issn.1009-2501.2025.03.008 Abstract （344）      PDF （1841KB）（762）       Knowledge map    Save AIM: To research the regulatory effects of Butein on lipid deposition and inflammation in non-alcoholic steatohepatitis (NASH). METHODS: HepG2 cells were divided into solvent control group (1‰ dimethyl sulfoxide) and different concentration of Butein groups (1, 3, 6, 12, 25, 50 μmol/L). The survival rate of HepG2 cells were detected, the low and high concentration groups of butein were determined. HepG2 cells were divided into solvent control group (1‰ DMSO), model group (induction with 1 mmol/L free fatty acids in vitro), low and high concentration of Butein groups. After 24 hours’ cell culture in each group, expression of triglyceride (TG), lipid synthesis-related factors SREBP-1c, FAS, SCD-1, lipid oxidation-related factors PPARα, CPT1A, MLYCD, and inflammatory factors TNF-α and MCP-1 in each group were detected. The model of NASH was constructed on C57BL/6J mouse by methionine choline deficiency diet (MCD). Normal diet group (ND group), model group (MCD group), low dose (100 mg·kg-1·d-1) and high dose (200 mg·kg-1·d-1) of Butein groups were established. After 4 weeks of feeding, pathological changes of liver tissues in each group were observed, contents of liver and serum TG and TC in each group were detected, and protein expression levels of lipid synthesis-related factors SREBP-1c, FAS, SCD-1 and lipid oxidation-related factors PPARα, CPT1A,  ACOX1 and MLYCD, inflammatory factors TNF-α and MCP-1in liver tissues were detected. RESULTS: Compared with solvent control group, Butein inhibited HepG2 cell growth when the concentration was ≥12 μmol/L (P<0.05). Make 5 and 10 μmol/L as low and high concentration groups, respectively. Compared with the solvent control group, the intracellular TG content of HepG2 cells in butein group was significantly lower (P<0.05). Compared with the model group, mRNA expressions of SREBP-1c, FAS, and SCD-1 was significantly lower (P<0.05), while mRNA expression of PPARα, CPT1A, and MLYCD was significantly higher (P<0.05), mRNA expression of TNF-α, MCP-1 was significantly decreased (P<0.05) in high-concentration butein group. Compared with the model group, the expression of SREBP-1c, FAS, SCD-1, MCP-1, TNF-α protein decreased and the expression of PPARα, CPT1A, MLYCD protein increased in the high concentration group. Compared with ND group, liver histological sections of MCD group showed obvious fat accumulation and inflammatory cell infiltration. Compared with the MCD group, the pathological manifestations of fat accumulation and inflammatory cell infiltration in the liver tissue of the butein groups were significantly improved, and the contents of TG and TC in the liver tissue of the butein groups were significantly decreased (P<0.05), while the protein expressions of PPARα, CPT1A, ACOX1, MLYCD were increased, and the protein expressions of SREBP-1c, FAS, SCD-1, TNF-α and MCP-1 were decreased in butein groups. CONCLUSION: Butein can improve lipid deposition and inflammation in NASH livers. Its mechanism may be to reduce the expression of lipid synthesis-related factors, enhance the expression of lipid oxidation-related factors, and reduce the expression level of inflammatory factors. Related Articles | Metrics

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Clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra time window TU Hanming, XU Guoqiang, CHEN Yongkang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (3): 398-403.   DOI: 10.12092/j.issn.1009-2501.2025.03.013 Abstract （342）      PDF （694KB）（449）       Knowledge map    Save AIM: To investigate the clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra-time window. METHODS: A total of 100 patients with ACI beyond time window admitted to our hospital from January 2021 to January 2023 were randomly grouped into the control group (50 cases, treated with stent thrombectomy) and the study group (50 cases, treated with tirofiban and butylphthalide combined with stent thrombectomy), clinical data of patients were collected, and the clinical efficacy, blood lipid levels, coagulation function, neurological function, quality of life, and incidence of adverse reactions were compared between the two groups. RESULTS: Compared with the control group, the total effective rate of the study group obviously increased (P<0.05). Before treatment, there was no obvious difference between the two groups in triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), fibrinogen (FIB), NIHSS score and Barthel index scale (BI) score of patients with ACI beyond time window (P>0.05). After treatment, the TG, TC, LDL-C, FIB, D-D, and NIHSS score of ACI patients in both groups decreased (P<0.05), while HDL-C, PT, APTT, and BI score increased (P<0.05), and the above indicators improved more obviously in the study group (P<0.05). There was no obvious difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of tirofiban and butylphthalide with stent thrombectomy in the treating ACI beyond time window has a definite effect, which can improve the blood lipid level, coagulation function and neurological function of patients, and help to improve the quality of life of patients, with good safety. Related Articles | Metrics

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Research and progress in the treatment of cardiovascular diseases with metabolic drugs SUN Min, WANG Hongya, HE Hongbo, ZHU Zhiming, GAO Peng Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (7): 984-997.   DOI: 10.12092/j.issn.1009-2501.2025.07.014 Abstract （341）      PDF （798KB）（2583）       Knowledge map    Save Cardiovascular disease (CVD), as one of the diseases with the highest morbidity and mortality rates globally, has always been a focus of medical research. In recent years, with a deeper understanding of the pathogenesis of CVD, novel metabolic drugs have demonstrated great potential in its treatment. These novel drugs regulate multiple aspects of cardiovascular metabolism, including reducing blood glucose and lipid levels, inhibiting inflammatory responses, and protecting vascular endothelial cells, thereby providing new strategies for the prevention and treatment of CVD. In terms of lowering blood glucose levels, SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and Metformin, as clinically commonly used drugs, have been proven to be beneficial for the prevention and treatment of CVD, regardless of the presence or absence of diabetes. For lipid regulation, PCSK9 inhibitors and Ezetimibe, as newly developed lipid-lowering drugs, not only reduce serum low-density lipoprotein cholesterol levels but also directly protect the cardiovascular system from damage. The development and application of these drugs have not only improved the treatment outcomes of CVD but also provided patients with more therapeutic options. Related Articles | Metrics

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Mechanism of total flavonoids of Carthamus tinctorius L.against hepatic fibrosis based on LC-MS/MS combined with network pharmacology and pharmacology experiments LI Mingqi, WANG Yinghe, ZHAO Xiaolu, BAO Xiaomei, YUE Xin, REN Guiqiang, MA Yuehong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 586-598.   DOI: 10.12092/j.issn.1009-2501.2025.05.002 Abstract （340）      PDF （5346KB）（137）       Knowledge map    Save AIM: To elucidate the pharmacodynamic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L., to explore their key targets and related pathways, and to clarify their mechanism of action against hepatic fibrosis. METHODS: The total flavonoids of Carthamus tinctorius L. were determined by LC-MS/MS and analysed for their compositions; the active ingredients were screened by TCMSP database, SWISS ADME database and literature search; the targets related to total flavonoids of Carthamus tinctorius L. were screened by Swiss Target Prediction database; and the targets related to hepatic fibrosis were screened by GeneCards database; the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L. were obtained by taking the intersection of Venny.2.1.0; the protein interactions were analysed by STRING database; the visualization analysis was carried out by Cytoscape software; the GO function and KEGG pathway analysis was carried out by Metascape platform; and molecular docking was verified by using AutoDock software for the core targets and active ingredients. The mechanism of anti-hepatic fibrosis of total flavonoids of Carthamus tinctorius L. was verified by animal model and in vitro cell experiments. RESULTS: A total of 41 flavonoid components were identified in Carthamus tinctorius L. Through the network pharmacological analysis, 149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L. were obtained, including 23 core targets.The GO enrichment analyses involved a total of three aspects, namely, biological process (BP), cellular component (CC), and molecular function (MF). KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the development of hepatic fibrosis. Molecular docking verified that the active ingredients Quercetin, Acacetin and Glabridin were tightly bound to Akt1 and HIFIA, respectively. In animal model experiments, it was observed by HE and Masson staining that fibroplasia was reduced, collagen deposition was reduced, inflammatory cell infiltration was reduced, and fibrotic liver tissues were improved in total flavonoids of Carthamus tinctorius L. administration group. In isolated cell experiments: Western blotting results suggested that total flavonoids of Carthamus tinctorius L. could decrease the hepatic fibrosis marker factor α-SMA, Collagen1 (P<0.01) and PI3K, Akt protein expression (P<0.01). CONCLUSION: Total flavonoids of Carthamus tinctorius L. exerted anti-hepatic fibrosis effects through multi-components, multi-targets and multi-pathways, and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway. Related Articles | Metrics

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Research progress on pharmacokinetic interactions of sodium-glucose co-transporter 2 inhibitors DENG Yanru, CAO Gexi, LI Ying, LI Yajing, DONG Zhanjun Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 570-576.   DOI: 10.12092/j.issn.1009-2501.2025.04.016 Abstract （337）      PDF （651KB）（2099）       Knowledge map    Save Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of oral hypoglycemic drugs with definite hypoglycemic effects, low risk of hypoglycemia, cardiovascular protection, and kidney benefits. In recent years, SGLT2 inhibitors have been widely used in clinical practice, and their interactions with other drugs have gradually attracted attention. The SGLT2 inhibitors commonly used in China's clinic include canagliflozin, dapagliflozin, empagliflozin, ertugliflozin and henagliflozin currently, they are mainly metabolized by the phase Ⅱ metabolic enzyme uridine diphosphate glucuronosyltransferase (UGT), and various transporters are involved in the disposal of SGLT2 inhibitors in vivo. This article reviews the pharmacokinetic characteristics of different SGLT2 inhibitors mentioned above, as well as their pharmacokinetic interaction studies with various drugs such as statins, antineoplastic drugs, antimicrobials, nonsteroidal anti-inflammatory drugs and traditional Chinese medicine, in order to promote the safe and rational use of SGLT2 inhibitors in clinical practice. Related Articles | Metrics

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Exploring the mechanism of action of BLJZF in the treatment of lipid abnormalities LIU Gen, YANG Weidong, LI Jia, LIU Cong, HAO Xuliang Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 464-476.   DOI: 10.12092/j.issn.1009-2501.2025.04.004 Abstract （335）      PDF （3798KB）（161）       Knowledge map    Save AIM:To explore the mechanism of BLJZF in the treatment of abnormal lipid metabolism based on network pharmacology, molecular docking and in vivo animal experiments. METHODS:TCMSP database, Swiss Target Prediction database, STITCH database and literature search were used to collect and query the chemical composition information of BLJZF and the corresponding target of drug chemical composition. Disease targets of lipid abnormalities were collected through GeneCards and OMIM databases. Metascape database was used to analyze the gene ontology function and the Kyoto Encyclopedia gene and genome pathway enrichment of common intersection targets. Cytoscape software was used to construct the correlation network diagram of components and targets, so as to select major components and targets for molecular docking study. The hyperlipidemia model was induced by high fat diet, and the control group, model group, positive group and BLJZF group were set up. The serum lipid index contents of triglyceride (TG), total cholesterol (TC), low lipoprotein cholesterol (LDL-C) and high lipoprotein cholesterol (HDL-C) were detected after continuous administration for 4 weeks. The contents of oxidative stress index were detected: alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of liver tissue. RESULTS:A total of 25 components and 315 corresponding targets of BLJZF were obtained, 1729 targets of lipid abnormalities and 116 common targets of BLJZF, among which the core targets were AKT1, TNF, IL1β, CASP3, etc. GO and KEGG enrichment analysis suggested that BLJZF may play a role through the lipid and atherosclerotic pathway, PI3K-Akt, AGE-RAGE in diabetic complications and other signaling pathways. Molecular docking showed that most of the core targets had high binding activity with the active ingredients. Animal experiments showed that compared with model group, TC, TG, LDL-C, ALT, AST and MDA in BLJZF group were significantly decreased, HDL-C and SOD were significantly increased, and the degree of liver fat deformation was reduced.CONCLUSION: BLJZF has a therapeutic effect on lipid abnormalities. It can treat lipid metabolism abnormalities through multi-component, multi-target and multi-pathway, and provide reference for subsequent drug research on BLJZF. Related Articles | Metrics

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Construction of a comprehensive prediction and visualization system for drug resistance in pulmonary tuberculosis patients based on an improved machine learning model WANG Feng, LIANG Luhua, ZHAI Fei, LUO Xiaoling, XIANG Rongwu Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (5): 673-682.   DOI: 10.12092/j.issn.1009-2501.2025.05.011 Abstract （331）      PDF （3078KB）（413）       Knowledge map    Save AIM: To analyze the clinical value of predicting drug resistance in pulmonary tuberculosis patients based on improved machine learning models, and to build a visualization system for verification. METHODS: Retrospectively selected 1 025 pulmonary tuberculosis patients hospitalized in Zhuhai Sixth People's Hospital from March 2019 to March 2024 with drug sensitivity test results as the research object. According to the definition of drug-resistant tuberculosis, the patients were divided into 631 sensitive groups (drug sensitivity test results showed no drug resistance), 271 RR/MDR groups (meeting the definition of rifampicin resistant tuberculosis or multi drug resistant tuberculosis, but no drug resistance to any kind of fluoroquinolones), and 123 pre XDR groups (on the basis of multi drug resistant tuberculosis, and at the same time, drug resistance to any kind of fluoroquinolones). Analyze clinical data based on the improved machine learning model, help build a drug resistant tuberculosis prediction model, synchronously complete feature screening, conduct value analysis on the screened features, and build a visual system for verification. RESULTS: Three groups of patients with baseline data comparison shows: Age, Body mass index(BMI), basic treatment of classification, lung diseases, haemoptysis, second-line drug use history, damage to lung, with empty in all statistically significant difference between the three groups (P< 0.05); Based on the modified machine learning model, 8 variables were screened, which were history of second-line drug use, BMI, treatment classification, destructive lung, underlying lung diseases, cavitation, hemoptysis, and age. The modified machine learning model had the highest prediction accuracy compared with the traditional model, with AUC values of 0.9322 (RR/MDR prediction was positive class) and 0.9545 (pre-XDR prediction was positive class). CONCLUSION: The application of the improved machine learning model can help predict the occurrence of drug-resistant tuberculosis and assist the clinical formulation of more effective treatment plans. Related Articles | Metrics

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The world's first PD-1/VEGF bispecific antibody:ivonescimab SUN Caihong, HU Taotao, XIAO Xingxing, YUAN Mengnan, JIANG Simin, CHEN Yinqi, RUAN Guodong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (9): 1290-1296.   DOI: 10.12092/j.issn.1009-2501.2025.09.016 Abstract （331）      PDF （1036KB）（754）       Knowledge map    Save Ivonescimab is a humanized bispecific antibody targeting human vascular endothelial growth factor-A (VEGF-A) and programmed death protein-1 (PD-1). It was approved by National Medical Products Administration on May 24th, 2024, and can be used in combination with pemetrexed and carboplatin for locally advanced or positive EGFR gene mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This paper mainly introduces the research progress of the world's first PD-1/VEGF bispecific antibody ivonescimab, and summarizes the mechanism of action, pharmacokinetics, phase I-III clinical trials and drug safety. Related Articles | Metrics

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Qingre sanzhuo decoction treats hyperuricemia complicated with gouty arthritis via TLR4/Myd88/NF-κB signaling pathway CHENG Weigang, LI Haolin, YANG Juanjuan, BAI Qian, JING Luoyang, HU Lele, JIN Fangmei, WANG Haidong Chinese Journal of Clinical Pharmacology and Therapeutics    2025, 30 (4): 456-463.   DOI: 10.12092/j.issn.1009-2501.2025.04.003 Abstract （324）      PDF （1841KB）（206）       Knowledge map    Save AIM: To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuricaemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway. METHODS: Forty-eight SD male rats were randomly divided into blank, model, and colchicine groups (0.3 mg·kg-1·d-1), and Origre sanzhou decotion low, medium and highdosage groups (7.42, 14.85, 29.70 g·kg-1·d-1), which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxalate, which was used for the treatment of acute gouty arthritis combined with hyperuricemia. A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia, combined with the modified Coderre method. After 7 days of intervention, the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated, the blood uric acid (HUA) level of rats was determined by biochemical method, the histopathological and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining, and the serum levels of inflammatory factors, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β were determined by enzyme-linked immunosorbent assay (ELISA), and Western blotting was performed to determine the levels of inflammatory factors, TNF-α, and IL-1β. The protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88), and nuclear factor-κB (NF-κB) in the synovial tissues of the ankle joints of the rats were determined by Western blot method, and the mRNA expression of TLR4, Myd88, and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). RESULTS: Compared with the blank group, rats in the model group showed significantly lower ankle joint swelling (P<0.01), increased levels of HUA, disorganised synovial tissue structure, large number of inflammatory cells infiltration, and significantly higher serum levels of TNF-α, IL-6, and IL-1β (P<0.01), and the protein and mRNA expression levels of TLR4, Myd88, and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased (P<0.01). levels were significantly increased (P<0.01); compared with the model group, joint swelling was significantly reduced in the colchicine group, and the medium- and high-dose groups of Qingre sanzhuo decoction (P<0.05); synovial hyperplasia and inflammatory cell infiltration were improved in the colchicine group and the medium- and high-dose groups of Qingre sanzhuo decoction, and the HUA and the levels of TNF-α, IL-6, and IL-1β were significantly decreased in the dosing groups (P<0.05, P<0.01), and compared with the model group, the medium- and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4, Myd88, and NF-κB protein and mRNA (P<0.01). CONCLUSION: Qingre sanzhuo decoction reduces the release of inflammatory factors by inhibiting the TLR4/Myd88/NF-κB pathway, and plays a role in the treatment of hyperuricaemia combined with gouty arthritis. Related Articles | Metrics